In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens
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2022
Authors
Assaleh, Mohamed H.Jeremić, Sanja
Cvijetić, Ilija
Marinković, Aleksandar
Prlainović, Nevena
Article (Published version)
Metadata
Show full item recordAbstract
Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present paper, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospitals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) - an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, 1H and 13C NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic ac...ids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 µM for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 107 and 109. The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics.
Keywords:
3D QSAR / Acinetobacter baumannii / Antimicrobial activity / Cinnamic acid amides / ThiocarbohydrazonesSource:
Journal of Molecular Structure, 2022, 1262, 133016-Publisher:
- Elsevier B.V.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200135 (University of Belgrade, Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200135)
DOI: 10.1016/j.molstruc.2022.133016
ISSN: 0022-2860
WoS: 00080385060001
Scopus: 2-s2.0-85128382542
Institution/Community
Tehnološko-metalurški fakultetTY - JOUR AU - Assaleh, Mohamed H. AU - Jeremić, Sanja AU - Cvijetić, Ilija AU - Marinković, Aleksandar AU - Prlainović, Nevena PY - 2022 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5111 AB - Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present paper, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospitals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) - an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, 1H and 13C NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic acids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 µM for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 107 and 109. The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics. PB - Elsevier B.V. T2 - Journal of Molecular Structure T1 - In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens SP - 133016 VL - 1262 DO - 10.1016/j.molstruc.2022.133016 ER -
@article{ author = "Assaleh, Mohamed H. and Jeremić, Sanja and Cvijetić, Ilija and Marinković, Aleksandar and Prlainović, Nevena", year = "2022", abstract = "Antimicrobial-resistance (AMR) has become the greatest concern and highly challenging issue when treating nosocomial infections. The exigency to develop new potent compounds continues to increase worldwide, whereby derivatives of natural products are becoming more attractive. In the present paper, the microbiological assessment of a series of 12 cinnamide hydrazides, four of them completely novel, against clinically relevant pathogens has discovered several derivatives with promising in vitro activities against Acinetobacter baumannii, one of the most dreaded opportunistic pathogens in hospitals. The compounds were synthesized by combining one of three different natural acids (cinnamic, 4-chloro or 4-methoxy) with four monothiocarbohydrazones (MTCHs) - an important class of synthetic organic molecules. Their structure was confirmed by elemental microanalysis, as well as ATR-FTIR, 1H and 13C NMR spectra, with the addition of 2D NMR spectra for novel compounds. The hybrids of cinnamic acids and pyridine derivatives are particularly active compounds with the lowest MIC50 value of 10.4 µM for p-chloro cinnamic acid and acetyl pyridine derivatives. An alignment-independent 3D QSAR model identified pharmacophoric hotspots and suggested several structural modifications that might improve the potency of this class of compounds against A. baumannii. The compounds are strong iron-chelating agents forming complexes with a stability constant between 107 and 109. The synthesized derivatives represent a promising class of antibacterial compounds with activities comparable to the commonly used antibiotics.", publisher = "Elsevier B.V.", journal = "Journal of Molecular Structure", title = "In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens", pages = "133016", volume = "1262", doi = "10.1016/j.molstruc.2022.133016" }
Assaleh, M. H., Jeremić, S., Cvijetić, I., Marinković, A.,& Prlainović, N.. (2022). In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens. in Journal of Molecular Structure Elsevier B.V.., 1262, 133016. https://doi.org/10.1016/j.molstruc.2022.133016
Assaleh MH, Jeremić S, Cvijetić I, Marinković A, Prlainović N. In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens. in Journal of Molecular Structure. 2022;1262:133016. doi:10.1016/j.molstruc.2022.133016 .
Assaleh, Mohamed H., Jeremić, Sanja, Cvijetić, Ilija, Marinković, Aleksandar, Prlainović, Nevena, "In vitro activity of novel cinnamic acids hydrazides against clinically important pathogens" in Journal of Molecular Structure, 1262 (2022):133016, https://doi.org/10.1016/j.molstruc.2022.133016 . .